Gastroesophageal Refund Acid Control Therapy with H2 Receptor Blockers & PPIs

1.2 – “Gastroesopha “Gastroesophageal geal Re Refund”: fund”: Acid control therapy with H2 receptor blockers & PPIs Physiology • Parietal cells in the gastric mucosa are responsible for gastric acid production, secreting acid into the gastric lumen (“Pour-it-all” lemonade, with lemonade spilling into the lumen-like sidewalk). Acid is secreted via Na-K-ATPase pump, maintaining electrolyte balance to secrete H+ ions into the lumen (Lemonade pump on the side of the stand is secreting acidic lemonade; mom is adding a potassium-laden banana to mix it up a bit; operated by 3 Ⓟ batteries). • Gastrin (gas cans) stimulates parietal cells, primarily by way of stimulating Enterochromaffin-like (ECL) cells (tree with the “Enter Carefully” sign) → release of H2 (gas driven leaf blower has disturbed histamine bees on the ECL tree) → activation of H2 receptors (GsPCR) (kid holding honey pot with S-shaped handles is attracting bees) → stimulation of parietal cells (honey-pot boy is knocking over lemonade pitchers, spilling onto sidewalk). Gastrin has a much smaller direct stimulatory effect on the parietal cells. Gastrin is released from G-cells in response to vagal stimulation via cholinergic M3 receptors using gastrin-releasing peptide (GRP) (truck is releasing gas tanks, in response to GRP lever being pulled. Parked next to motorcycle with “Vegas” sticker in M3 spot). • Zollinger-Ellison syndrome is seen with gastrinoma, where excess gastrin production over-activates ECL cells (jumbo gas tank on the cancer crab lawnmower is over activating bees). Results in heartburn, diarrhea, GI bleed Rx • H2 blockers o cimetidine, ranitidine, famotidine, nizatidine (tie-dye shirts for -tidine suffix; 2 bee swatters for H2 blockers). o Reversibly bind to H2-receptors, inhibiting acid secretion from parietal cells. H2 receptor blockers have a strong effect on nocturnal acid secretion, but minimal effect on prandial secretion. Fast action & short duration make this class suitable for symptomatic relief. o Indications ▪ Can be used to treat GERD and ulcers (gastric & duodenal), although PPIs are preferred for both (girl gurgling lemonade while standing on a cracked sidewalk). o Adverse effects ▪ Cimetidine is notorious for adverse effects (tie-dyed kid in the cement) ▪ CYP450 inhibitor (beating up the car with the CYP-450 plates) ▪ Antiandrogen effects: Hyperprolactinemia (kid laughing milk out nose), gynecomastia (kid holding lids to his chest), impotence & decreased libido (floppy honey wand) ▪ Can cross BBB → confusion, dizziness, headaches, especially in the elderly ▪ Crosses placenta ▪ Cimetidine & ranitidine both →↓Crt secretion (although have no actual negative effects on GFR) • Proton pump inhibitors (PPIs) o omeprazole, lansoprazole, esomeprazole, pantoprazole, dexlansoprazole (“prize” sounds a bit like -prazole). o Form a covalent disulfide bond with Na-K-ATPase. By blocking the final common pathway to acid production, these are the most effective treatment for acid production, regardless of the etiology (girl scouts are blocking the lemonade pump). o Indications ▪ First line agents in GERD, with both erosive & non-erosive esophagitis (gargling girl) ▪ duodenal &, to a less extent, gastric ulcers (cracked sidewalk) ▪ Zollinger-Ellison syndrome ▪ stress ulcer treatment ▪ Part of routine H. pylori triple therapy (helicopter hat on girl scout). ▪ Clinically, often used for unexplained dyspepsia o Side effects: ▪ Up to 3x increased risk of C. diff infection (chocolate fountain). ▪ Increased risk of respiratory infections/PNA, both nosocomial & community acquired (dark lung shaped chocolate spots on scouts tee). Possibly d/t ↑levels of upper GI bacteria. Note that the evidence for this in the literature is relatively weak. ▪ Decreased absorption of calcium, magnesium, and iron, as all three rely on an acidic environment (electrolyte medals on wagon), all easily treated by supplementation. If untreated, may result in : • Exacerbation/cause of osteoporosis (termite-eaten wagon) • ↑risk of osteoporotic fractures (broken bone-shaped axel) • Hypomagnesemia (falling magnets) • Vitamin B12 deficiency • Octreotide (exogenous SST) o Endogenous somatostatin (SST) inhibits gastrin release (G-cells) & histamine (ECL cells). can be administered to manage some cases of excess acid production, notably in SST-sensitive gastrinoma (octagonal stop sign blocking irritation of bees).